HCID 58681881, compound → HCID 58681892, compound

HRID 10310Notes

Reaction equation

HRID 10310 reaction equation
[C:1]([O:5][C:6](=[O:46])[NH:7][N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]([F:41])[C:13]([N:28]3[CH2:32][CH2:31][C@H:30]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29]3)=[C:14]([F:27])[C:15]=2[NH:19]CC2C=CC=CC=2)[N:10]([CH:42]2[CH2:44][CH2:43]2)[C:9]1=[O:45])([CH3:4])([CH3:3])[CH3:2]>O1CCCC1.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6](=[O:46])[NH:7][N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]([F:41])[C:13]([N:28]3[CH2:32][CH2:31][C@H:30]([NH:33][C:34]([O:36][C:37]([CH3:39])([CH3:40])[CH3:38])=[O:35])[CH2:29]3)=[C:14]([F:27])[C:15]=2[NH2:19])[N:10]([CH:42]2[CH2:43][CH2:44]2)[C:9]1=[O:45])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 58681881HCID 58681881, compound

Product 1

HCID 58681892HCID 58681892, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

{7-[(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-benzylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 10 (0.435 g, 0.676 mmol) in tetrahydrofuran (20 mL) is hydrogenated at room temperature and atmospheric pressure over 20% palladium hydroxide on carbon (0.114 g) for 27 hours. The mixture is filtered through Celite, the solid is washed with chloroform, and the combined filtrates concentrated under vacuum. Purification by column chromatography (2:3 ethyl acetate/hexanes) gives {5-amino-7-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}-carbamic acid tert-butyl ester as a solid (0.284 g). 1H NMR (CDCl3): δ 6.61 (bs, 1H), 5.94 (bs, 2H), 4.82–4.69 (bd, 1H), 4.40–4.21 (m, 1H), 4.00–3.59 (m, 3H), 3.55–3.41 (m, 1H), 3.35–3.21 (m, 1H), 2.32–2.08 (m, 1H), 2.01–1.80 (m, 1H), 1.50 (s, 9H), 1.46 (s, 9H), 1.17–1.01 (m, 2H), 0.77–0.63 (m, 2H).

Workup

  1. customis hydrogenated at room temperature
  2. filtrationThe mixture is filtered through Celite
  3. washthe solid is washed with chloroform
  4. concentrationthe combined filtrates concentrated under vacuum
  5. customPurification by column chromatography (2:3 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c978877a17c84bafbb196b62c0e17983
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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